Work during the last year has demonstrated that the number of muscarinic receptors present in cultured heart cells may be modulated by treatment with muscarinic agonists. The number of muscarinic receptors as measured by binding of (3H)-QNB is decreased 65% after a 3-hour incubation with 10 to the minus 3rd power carbamylcholine. This decrease in receptor number corresponds to a marked loss of physiologic responsiveness to muscarinic agonists with only 35% inhibition of beating rate at 10 to the minus 3rd power carbamylcholine in cells pretreated with carbamylcholine compared to 100% inhibition for control cells. Those receptors remaining after treatment with carbamylcholine exhibit binding properties for (3H)-QNB similar to those in control cells. Studies of the mechanism of this decrease in receptor number are in progress. The effect of carbamylcholine on K ion permeability in cultured heart cells as measured by 42K ion efflux has been studied. Permeability increases two fold in control cells after treatment with 10 to the minus 3rd power carbamylcholine but only by 20% in cells subjected to prior treatment with carbamylcholine. Studies of the effects of medium conditioned by prior incubation with cultures of chick sympathetic ganglion cells on muscarinic receptor number, physiologic function and K permeability response will be undertaken shortly.